PSUN363 GCM2 variants in Parathyroid Carcinoma

Abstract Germline, in vitro activating GCM2 variants are notably overrepresented patients with primary hyperparathyroidism (PHPT), both the familial and sporadic settings. While increased compared general population, most individuals such population have a very low risk of developing PHPT. However, for those who do develop PHPT, degree to which harboring variant might impact disease severity remains unclear. An likelihood multigland involvement lower rate biochemical cure has been reported GCM2variant-positive as variant-negative patients. In context isolated hyperparathyroidism, one individual Y394S was developed parathyroid carcinoma (Guan, 2016) another parathyromatosis (Koh, 2021). family, carrying I383M, seen atypical adenoma (Canaff, 2022). No were noted two other kindreds included at least carcinoma, known causes FIHP had already ruled out (Cetani, 2019). Rare three carcinoma: K388E (Song, 2020) V382M also observed patient 2020). whole exome sequencing (WES) studies carcinoma. 45% cases subjected WES, germline specifically filtered during data analysis. remaining DNA unavailable, filtering would excluded common variants, Y282D, but rare may detectable. We sought determine frequency interest series 15 carcinomas by direct sequencing. sequence identified within C-terminal conserved inhibitory domain (CCID) GCM2, nor PHPT-associated Y282D found any our samples. Across all date, CCID detected 3 48 (6.25%) 4 56 (7.14%) cases. Our results demonstrating dearth combined absence malignancy overwhelming majority suggest exceedingly some be show higher penetrance. Given potential implications surveillance/monitoring approaches and/or surgical decision making, hypothesis that certain genetic environmental contexts associated more severe clinical phenotypes merits further investigation. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30